Innovation in the Biopharmaceutical Pipeline

Executive Summary The U. S. innovative biopharmaceutical industry leads the world in the development of new medicines: over the past decade some 300 new prescription medicines have been approved for use by the U. S. Food and Drug Administration (FDA). Together, these innovations have contributed to a range of new treatments resulting in improvements in the length and quality of life and reduced disease burden for individuals and society. However, the need for innovative new therapies for some of the most costly and challenging diseases and conditions has never been greater.

This study presents data on two types of potential new treatments in the research and development pipeline: ? ? New medicines in development, or new molecular entities (NMEs) – data for which are referred to in this report as new “products”; and New molecule-indication combinations in development (which may be NMEs or new indications for medicines previously approved by the FDA) – data for these unique molecule-indication combinations are referred to in this report as “projects. ”

In both cases, we have focused our review on those activities that have advanced to the clinical testing stage in human volunteers, except where otherwise noted. In addition to excluding preclinical research, several other types of innovative activities were beyond the scope of this report. While new and enhanced methods of delivery and new formulations also represent new treatment options for patients and their health care providers, the study’s scope was limited to new molecules and new molecule-indication combinations.

Similarly, post-approval research and Phase IV trials were beyond the scope of the analysis. The study is based on a review of data from 1986 onward from EvaluatePharma, a proprietary commercial database containing information on over 4,500 companies and 50,000 products, complemented by data on clinical trials found on ClinicalTrials. gov, and on orphan drug designations in the FDA Orphan Drug Product database. Developing a new medicine is a long and complex process, with risk of failure at each step.

While thousands of new medicine candidates are screened in the laboratory, only one may eventually result in an FDA-approved medicine, after 10 to 15 years of testing, development, and review. It is impossible to predict which of the specific products or projects described in this report will eventually proceed all the way to FDA approval and ultimately to patients. Key findings from the report include the following: ? ? The pipeline of drugs contained over 5,400 products in clinical development (i.

e. , those which have advanced to clinical testing in human volunteers, but have not yet been launched). Taking into account the fact that a single molecule may be undergoing or have undergone clinical trials in more than one indication, there were nearly 8,000 projects in clinical development (that is, unique molecule-indication combinations; e. g. , a particular drug in clinical trials for use in Alzheimer’s disease and schizophrenia would be counted as one product and two projects).

Development projects were distributed across many therapeutic areas, from cancer to cardiovascular disease and diabetes, to neurology. For example, more than 1,600 projects were under way in neurology alone. INNOVATION IN THE BIOPHARMACEUTICAL PIPELINE ? A high percentage of NME-focused development activities were potentially first-in-class (i. e. , those described by a unique pharmacological class distinct from those of any other marketed products): 78 percent of projects in Phase I, 69 percent in Phase II, and 45 percent in Phase III were potentially first-in-class.

Only one molecule in a given class can eventually win first-in-class designation; however, it cannot be known in advance which molecule will proceed through clinical testing and be approved first. There were particularly high percentages of potential firstin-class medicines in neurology (84 percent), psychiatry (80 percent), cancer (80 percent), and diabetes (79 percent). As of October 2011, 1,795 projects with an orphan disease designation by the FDA were in development.

These activities address a broad range of diseases and conditions from enzyme storage disorders to rare cancers. Orphan diseases individually affect fewer than 200,000 people in the U. S. , but taken together are estimated to affect some 25 million people. A number of potential medicines in development would provide new clinical options for patients with diseases for which no new therapies have been approved for many years. An analysis of 15 selected diseases with no approvals in the past 10 years identified over 400 projects in development.

Personalized medicine approaches are receiving a growing emphasis in development. A separate analysis of data on only Phase III and Phase IV U. S. clinical trials involving the use of molecular biomarkers (i. e. , characteristics that can guide treatment and diagnosis and are integral to personalized medicine) identified 155 personalized medicine trials that were initiated on or before January 2009. A range of novel scientific approaches to address various diseases and conditions were being pursued.

Broad classes of scientific “platforms” readily identifiable in the dataset revealed: 245 projects using cell therapy; 127 projects using antisense RNA interference therapy (an approach that targets RNA, which carries genetic information that creates proteins, rather than proteins themselves); 102 projects using monoclonal antibodies joined to cytotoxic agents to target tumor cells while sparing nearby healthy cells; and 99 projects using gene therapy. ? ? ? ? INNOVATION IN THE BIOPHARMACEUTICAL PIPELINE.

The Continuing Need for New Medicines Study Objectives In Brief: The Drug Discovery and Development Process Describing The Pipeline: The Many Dimensions of Biopharmaceutical Innovation Analysis Results A. B. C. D. E. F. Total Number of Medicines in Development, by Therapeutic Area Potential First-in-Class Medicines in Development Orphan Diseases Therapies Targeting Diseases with No Recently Approved Therapies Personalized Medicines in Development Novel Scientific Strategies 1 1 2 5 7 7 10 14 16 18 22 26 27 28 Conclusion Appendix A: Methodology, Definitions, and Sources Appendix B: Indications by Therapeutic Area.

INNOVATION IN THE BIOPHARMACEUTICAL PIPELINE THE CONTINUING NEED FOR NEW MEDICINES The U. S. biopharmaceutical industry leads the world in the development of new medicines. Consistent with the Congressional Budget Office’s finding that this sector is one of the nation’s most researchintensive, 1 the most recent annual survey of members of the Pharmaceutical Research and Manufacturers of America reports that its members invested almost $50 billion in 2011 in discovering and developing new medicines, representing the majority of all biopharmaceutical research and development (R&D).

Spending in the U.S. 2 Biopharmaceutical innovation has led to improvements in length and quality of life and reduced disease burden for individuals and society. New medicines have transformed patients’ health and quality of life in many areas, from heart disease to HIV/AIDS to cancer to mental health disorders. 3 For example, since the introduction of multiple effective therapies against HIV/AIDS starting in 1995, the HIV/AIDS death rate has fallen by 83 percent in the United States.

4 Given many groundbreaking advances in the scientific understanding of the underlying mechanisms of disease, the future holds great promise for further improvements in human health and the potential to reduce the socioeconomic burden of disease. The need for continued development of new treatments is also great, given demographic trends and public health considerations. For instance, the direct costs to all payers of caring for those with Alzheimer’s disease, including out-of-pocket costs to patients and their families, is estimated to increase five-fold, from $172 billion in 2010 to $1.

1 trillion in 2050, unless new treatments are found that delay its onset or slow its progression. 5 STUDY OBJECTIVES This report aims to provide descriptive information about the current pipeline of medicines in development with the potential to aid U. S. patients from a range of different data-driven perspectives. It focuses on medicines that have entered clinical testing in human volunteers and are therefore closer to launch than those still in preclinical development or in animal testing, except where otherwise noted.

The drugs in clinical testing with human volunteers today are the therapies that have the potential to drive new treatments and potential cures over the next five to 10 years for a range of diseases and conditions, from diabetes and cardiovascular disease to rare diseases and disorders for which an effective therapy has yet to be developed. 1 2 3 Congressional Budget Office, “Research and Development in the Pharmaceutical Industry” (2006). Pharmaceutical Research and Manufacturers of America, PhRMA Annual Membership Survey (Washington, D.

C. : PhRMA, 2012). See, e. g. , CASCADE Collaboration, “Determinants of Survival Following HIV-1 Seroconversion After Introduction of HAART,” The Lancet, 362 (2003):1267–1274; F. R. Lichtenberg, “The Expanding Pharmaceutical Arsenal in the War on Cancer,” National Bureau of Economic Research Working Paper No. 10328 (Cambridge, MA: NBER, February 2004); Tufts Center for the Study of Drug Development, “Personalized Medicine Is Playing a Growing Role in Development Pipelines,” Impact Report 12 (Nov/Dec 2010): 6.

U. S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics, Health, United States (2003): With Chartbook on Trends in the Health of Americans (Hyattsville, MD: HHS, 2003); S. L. Murphy, J. Xu, and K. D. Kochanek, “Deaths: Preliminary Data for 2010,” National Vital Statistics Reports 60, no. 4 (Hyattsville, MD: National Center for Health Statistics, January 2012): 17 (accessed 10 March 2012).

Alzheimer’s Association, “2012 Alzheimer’s Disease Facts and Figures” (2012). 4 5 Page 1 INNOVATION IN THE BIOPHARMACEUTICAL PIPELINE IN BRIEF: THE DRUG DISCOVERY AND DEVELOPMENT PROCESS Developing a new medicine is a long and complex process, with risk of failure at each step. It has been estimated that the average cost to yield a single FDA-approved drug is approximately $1. 2 billion (including the cost of development failures), 6 and the entire research and development and FDA approval process time is between 10 and 15 years.

7 Discovery and preclinical testing Prior to testing in humans, a new drug candidate is considered to be a preclinical or discovery (rather than development) project. The focus of preclinical testing is to determine whether the drug is safe enough to use in human volunteers and whether it exhibits sufficient pharmacological activity to merit further investigation. If the candidate medicine meets these criteria, the company files an Investigational New Drug (IND) application with the FDA to permit testing in humans. Clinical testing in human subjects Drug development is staged in three successive phases.

A Phase I clinical trial is typically conducted in a small number of healthy volunteers, typically fewer than 100, to determine the safety, tolerability, and pharmacokinetics and pharmacodynamics of the drug (how the drug behaves in the body and the relationship between the drug’s chemical structure and its effects on patients). If a drug successfully passes Phase I testing, then Phase II clinical trials are conducted in patient volunteers to assess the efficacy and dose response of the drug. Phase II trials typically may enroll 100 to 500 patients and identify common, short-term drug treatment side effects.

Drugs that appear to be both safe and efficacious in Phase I and II clinical testing are next tested in larger randomized, controlled Phase III clinical trials, which might enroll 1,000 to 5,000 patients (or more) across numerous clinical trial sites around the world. From enrollment to completion, Phase III trials may take years to complete and cost many millions of dollars. Regulatory authorities in the U. S. and other countries typically require positive data from two Phase III trials to support a submission for market approval.

Regulatory review and approval If the trials are successful, the data collected from preclinical studies and the full set of clinical trials are submitted to the U. S. Food and Drug Administration (FDA) for review in the form of a New Drug Application (NDA) or Biologic License Application (BLA) (in the U. S. ). If the drug is approved, the manufacturer may market it for the approved indications. 6 In 2005 dollars, when capitalized using an 11. 5% discount rate, and including the cost of development failures. J. A. DiMasi and H. G.

Grabowski, “The Cost of Biopharmaceutical R&D: Is Biotech Different? ” Managerial & Decision Economics (2007) 28:469–479. J. A. DiMasi, “New Drug Development in U. S. 1963–1999,” Clinical Pharmacology & Therapeutics 69, no. 5 (2001): 286–296; M. Dickson and J. P. Gagnon, “Key Factors in the Rising Cost of New Drug Discovery and Development,” Nature Reviews Drug Discovery 3 (May 2004): 417–429; J. A. DiMasi, R. W. Hansen, and H. G. Grabowski, “The Price of Innovation: New Estimates of Drug Development Costs,” Journal of Health Economics 22 (2003): 151–185. 7.

INNOVATION IN THE BIOPHARMACEUTICAL PIPELINE Post-approval research and monitoring Phase IV clinical trials are often conducted to test the long-term safety and efficacy characteristics of approved drugs and may be required by the FDA as a condition of approval. (This report does not reflect data on post-approval research and thus does not include a review of Phase IV trials. ) As noted, while many thousands of compounds are screened in the lab, only one of these thousands may result eventually in an approved medicine, after many years of testing and development.

The vast majority are eliminated prior to testing in human beings through laboratory screening and preclinical testing. Others have calculated that the probability of a drug that begins the next step, clinical trials in human subjects, proceeding all the way to market launch is approximately 20 percent. 8 Because most potential medicines in development will never proceed through rigorous screening and testing procedures all the way to launch, most R&D expenditures go toward projects that do not survive the long testing, development, and approval process.

As a result, R&D costs must be borne by the very few projects that proceed all the way to FDA approval and benefit patients. Overview of R&D Challenges Debate continues over the long-term outlook for medical innovation, with industry analysts and others expressing differing perspectives on the potential for continued innovation across the biopharmaceutical development pipeline, various indicators of R&D productivity such as the relationship between the level of R&D spending and eventual pipeline approvals, and whether the historical pace of new drug innovation can be sustained.

An increase in the level of real investment in R&D, coupled with a flat to declining number of annual new molecular entity (NME) approvals by the FDA, has led to concerns among some about the level of pipeline productivity over time (i. e. , “how much” innovation is being produced per dollar spent on R&D). Figure 1 presents figures for annual and cumulative new drug approvals by the FDA’s Center for Drug Evaluation and Research (CDER), including both NMEs and BLAs. 8 For compounds first tested in human subjects from 1993 to 2004. J. A.

DiMasi et al. , “Trends in Risks Associated with New Drug Development: Success Rates for Investigational Drugs,” Clinical Pharmacology & Therapeutics| vol. 87, no. 3 (March 2010), 272–277. Page 3 INNOVATION IN THE BIOPHARMACEUTICAL PIPELINE Figure 1. Annual and Cumulative New Drug Approvals Since 2000 350 Annual Approvals Cumulative Approvals Since 2000 305 275 254 229 New Drug Approvals Per Year 300 250 205 200 187 165 145 109 150 100 82 58 29 29 29 2001 24 2002 27 2003 36 2004 20 2005 22 2006 18 2007 24 2008 25 2009 21 2010 30 2011.

50 0 2000 Notes: New drug approvals include New Molecular Entities (NMEs) and biologic license applications (BLAs). Source: Asher Mullard, “2011 FDA Drug Approvals,” Nature Reviews Drug Discovery 11, no. 2 (February 1, 2012): 91–94. Others have examined factors affecting the cost, duration, and uncertainties associated with clinical trials, which continue to challenge the current drug development economic model. (See “R&D Challenges: Increasing Procedure Intensity in Clinical Trials.”)

In response, scientists from industry, government, and academia have been working to develop new tools and methods in order to improve R&D efficiency, including such approaches as computer-based models to predict how a candidate drug is absorbed, distributed, and eliminated from the body. Better predictive models would improve the efficiency of the drug development process by either narrowing the patient population where the drug has the best chance of success, or eliminating candidate drugs before risky and costly clinical trials begin.

As a result, candidate drugs in clinical trials would have a better chance of working, and fewer clinical trials might be needed to establish safety and efficacy. In addition, researchers are collaborating on pre-competitive research in areas such as biomarkers in order to accelerate research progress. Page 4 INNOVATION IN THE BIOPHARMACEUTICAL PIPELINE R&D Challenges: Increasing Procedure Intensity in Clinical Trials A recent analysis found that clinical trials are becoming increasingly complex in terms of the number of procedures and total clinical staff time involved and the challenge of enrolling and retaining patient volunteers.

The four-year period between 2004 and 2007 saw an increase of 49 percent in median procedures per clinical trial as compared with the previous four-year period from 2000 to 2003 and a decrease of 21 percent in patient volunteer enrollment rates (as a result of more demanding patient eligibility criteria). 1 If not offset, these developments may lead to future increases in the expense and time required to successfully develop new drugs. 1 Tufts Center for the Study of Drug Development, “Rising Protocol Complexity, Execution Burden Varies Widely by Phase and TA,” Impact Report 12, no.

3 (May/June 2010). DESCRIBING THE PIPELINE: THE MANY DIMENSIONS OF BIOPHARMACEUTICAL INNOVATION This report presents information on compounds that have advanced to the clinical testing stage in human volunteers, except where otherwise noted. Data on them are grouped in various ways (e. g. , by indication or therapeutic area, such as all diabetes drugs), but it is impossible to know in advance which specific development projects will ultimately proceed to complete development, be launched in the U. S. , and be available to patients as new treatments.

Most projects, particularly in the early stages of development, will not surmount all the hurdles placed before them. These data have been supplemented in some cases with information from the literature to provide additional insights on selected trends and examples. Given the impossibility of predicting the eventual clinical value of today’s many and varied development efforts years in the future, this report provides a number of different metrics describing the drug development pipeline, including: ?? ? ? ? ?

Total numbers of medicines in development, by therapeutic area (e. g. , cardiovascular disease, diabetes, psychiatry, and neurology); Potential first-in-class medicines, those that introduce a new mechanism of action or pharmacological class for attacking a given disease or condition; Medicines targeting rare “orphan diseases” affecting 200,000 or fewer patients in the U. S. (e. g., amyotrophic lateral sclerosis, or Lou Gehrig’s disease);

Medicines targeting diseases for which there have been no recently approved therapies; Medicines that incorporate a “personalized medicine” approach, tailored to specific subpopulations of patients based on molecular or genetic characteristics; and Medicines that are among the first to apply new scientific strategies to address disease and that may hold promise in enabling other future therapies previously impossible with existing technologies (e.g. , gene therapy, therapeutic vaccines for cancer).

Each of these perspectives provides a different view of the drug development pipeline and its potential to address challenging diseases and patient needs. Some of these measures relate to the numbers of therapies, others to the types of therapies or patients who may benefit from them. The analysis begins Page 5 INNOVATION IN THE BIOPHARMACEUTICAL PIPELINE.

with the most straightforward descriptive measures of the drug pipeline, simple counts of new therapies in development by phase of development, and by therapeutic area. These measures are supplemented with several others that provide information on approaches that may advance treatment and the types of diseases that would be affected should the drug proceed all the way to FDA approval and launch and the potential clinical value to patients.

(i.e. , whether the therapy may benefit “orphan populations” that often have few therapeutic alternatives available, or whether the therapy has the potential to be a “first-in-class” drug in a given therapeutic area or provide a treatment where there have been no recent other approvals), noting that it is not possible to fully assess the clinical value of a drug so early in its life cycle (i. e. , while the drug is still in development).

This report also presents data on whether drug development followed a “personalized medicine” approach and whether the therapy would be among the first to apply certain new scientific approaches that might open up new ways to target diseases (e. g. , gene therapy, therapeutic vaccines for cancer). The scientific approaches reflected are not exhaustive and do not represent a value judgment or prediction of the potential future scientific and clinical value of these identified novel scientific approaches as opposed to others.

Thousands of drug candidates are in development, and an individual review of each would have been impossible. Rather, we acknowledge that we have only scratched the surface in selecting a few more readily identifiable, highly novel approaches that are systematically identifiable in the data source used for the analysis. There are surely many others that are equally important (or possibly more important) sources of innovation in terms of “opening the door” to other future novel therapies for patients, but which were not readily or systematically identifiable in our data sources.

Results are generally for drugs in development or under FDA review as of December 12, 2011, unless otherwise noted. While our interest is in drugs in development for the U. S. market with the potential to aid U. S. patients, it is difficult to identify ex ante which drugs in development may eventually be submitted for FDA approval; development activity is inherently global, although regulatory review, launch, and marketing are market-specific.

Because most drugs are intended for marketing in the U. S., the largest drug market in the world, we have not excluded any drugs in clinical development (i. e. , in Phases I, II, or III). However, in any counts of drugs currently in regulatory review, we have excluded drugs that were not filed with the FDA. A description of the methodology, definitions, and sources used is provided in Appendix A. Page 6 INNOVATION IN THE BIOPHARMACEUTICAL PIPELINE ANALYSIS RESULTS A.

Total Number of Medicines in Development, by Therapeutic Area As illustrated in Figure 2 below, as of December 2011, there were more than 17,000 projects (i. e., unique molecule-indication combinations) in clinical development and a total of about 12,000 products (or new medicines that would be submitted for FDA review as NMEs) in development. 9 ?

Preclinical research accounted for the highest number of projects (over 9,000) and potential new medicines (over 6,500). These figures are likely an underestimate, as many preclinical research activities may not yet have been the subject of news or analyst coverage or may only be known to the researchers and manufacturers involved, and therefore would not yet be reflected in the dataset.

Over 5,400 new products were in clinical development (defined in this report as products in Phase I, II, III, or having been filed with the FDA, or approved by the FDA, but not yet on the market in the U. S. ). Since a single product may be investigated for multiple indications, and because the data include additional indications for products already approved and on-market, the number of pipeline projects in clinical development is larger, or about 8,000. ?

Consistent with previous studies showing high attrition rates between Phase II and the much more expensive and lengthy Phase III clinical trial stage, there were many fewer compounds at each progressive phase of development. Whereas there were 2,329 molecules recorded in Phase II clinical trials, there were only 833 products in Phase III trials. A total of 82 products in the dataset had completed Phase III clinical trials and had either been filed with the FDA or were approved by the FDA, but had not yet been launched in the U. S. 9.

As noted earlier, this report distinguishes between products and projects, reporting data for both where appropriate. We use the term “product” to denote a unique molecule or NME in development (e. g. , a particular recombinant protein). We use the term “project” to refer to unique product and indication combinations (e. g. , a particular recombinant protein for colorectal cancer, rather than breast cancer). In the counts we present of projects, a single molecule being investigated in multiple indications will be counted once for each indication, reflecting the fact that distinct clinical trial activity is required for each indication.

When showing counts of products, a given molecule will be counted only once, and only if it has not yet been approved by FDA and is on-market. In the case of projects to test additional clinical indications for products already approved by FDA and on the market, therefore, each indication is counted as a separate project, and the molecule itself is not included in the product count (if it is already approved and on-market). Page 7 INNOVATION IN THE BIOPHARMACEUTICAL PIPELINE Figure 2. Distribution of Products and Projects by Phase.

Phase Preclinical/Research Project Clinical Development Phase I Phase II Phase III U. S. Filed/Approved But Not Yet Marketed Total Number of Projects 9,090 7,982 3,025 3,764 1,099 94 17,072 Number of Products 6,551 5,408 2,164 2,329 833 82 11,959 Notes: Projects and products are limited to NMEs, as defined by EvaluatePharma. U. S. Filed/Approved But Not Yet Marketed phase projects must have a reported FDA approval date. Filed projects limited to those filed with the FDA. Products are unique NMEs; projects are unique NME-indication combinations.

Source: Authors’ calculations, using EvaluatePharma data. Figure 3 presents the number of projects in clinical development by indication or therapeutic area. While there were projects in development across the therapeutic spectrum, certain therapeutic areas, such as various cancers, infectious diseases, and neurology, showed the greatest number of development projects, perhaps reflecting scientific advances in our understanding of the basis of these diseases and potential novel approaches and different mechanisms for disease intervention.

Although neurological conditions historically have been among the most difficult for which to develop effective and safe new therapies due to the complexity of the scientific and clinical challenge, neurology was the third most common category of drugs in preclinical development, and the third most common in Phase III clinical trials. High numbers of drugs were also in development for cancer and infectious disease – including those targeting HIV/AIDS.

Clinical trials in diseases like cancer, neurology, and respiratory disease were more heavily weighted toward earlier-phase trials – there were approximately four times as many Phase II trials as Phase III trials under way; for others such as blood diseases, infections, and reproductive conditions, there were twice as many. There was a higher ratio of projects to products in cancer, perhaps reflecting the growing understanding of the disease at a molecular-mechanism rather than organ-system level; compounds were being investigated for multiple cancers that have similar underlying mechanisms, but which may affect different organ systems.

(See “Mapping Common Cancer Pathways: Genetic Profiling of Colorectal Cancer and Other Tumors May Reveal New Cancer Treatments. ”) Immunology also had a higher ratio of development projects to products, reflecting that these conditions share common pathways, so drugs may be effective across multiple indications, thus resulting in a higher number of projects in development per product. Page 8 INNOVATION IN THE BIOPHARMACEUTICAL PIPELINE Figure 3. Distribution of Products and Projects by Therapeutic Area and Phase Number of Projects by Phase U. S. Filed / Approved But Not Yet Marketed Therapeutic Area.

Preclinical / Research Project Phase I Phase II Phase III Total Projects Total Products Blood Cancer Total Cancer, Blood Cancer, Miscellaneous cancer Cancer, Solid tumors, Bladder Cancer, Solid tumors, Breast Cancer, Solid tumors, Colorectal Cancer, Solid tumors, Lung Cancer, Solid tumors, Melanoma Cancer, Solid tumors, Prostate Cancer, Solid tumors, Other Cardiovascular Diabetes Gastrointestinal Hepatic & biliary HIV & related conditions Hormone Immunology Infections Miscellaneous Musculoskeletal Neurology Psychiatry Reproduction Respiratory Sensory Organs Skin Surgery Urinary tract Total Projects Total Products.

188 2,400 239 922 21 118 81 95 54 119 751 434 349 232 55 141 19 747 1,295 424 435 1,043 177 76 400 319 255 33 68 9,090 6,551 58 1,265 243 126 10 45 48 65 51 53 624 128 103 78 23 62 6 126 304 107 102 256 85 32 123 47 73 13 34 3,025 2,164 82 1,507 277 59 20 119 81 156 75 92 628 230 132 116 31 48 8 123 289 66 148 273 120 60 198 120 154 16 43 3,764 2,329 41 288 55 14 4 20 15 34 12 18 116 85 43 49 3 16 7 45 135 50 52 74 35 28 47 35 44 9 13 1,099 833 4 13 4 2 1 1 1 1 3 7 3 6 2 4 22 9 1 7 4 2 4 3 1 2 94 82 373 5,473 818 1,123 56 302 226 350 193 283 2,122 884 630 481 112 269 40 1,045 2,045 656 738 1,653 417 200 770 525 529 72 160 17,072.

266 3,436 383 865 27 95 63 142 105 217 1,539 650 412 349 69 204 29 731 1,586 590 454 1,247 303 157 485 399 412 67 113 11,959 Notes: Projects and products are limited to NMEs, as defined by EvaluatePharma. U. S. Filed/Approved But Not Yet Marketed phase projects must have a reported FDA approval date. Filed projects limited to those filed with the FDA. Products are unique NMEs; projects are unique NME-indication combinations. Counts by phase may include some duplicates due to co-promotion/codevelopment of products. Source: Authors’ calculations, using EvaluatePharma data.

Page 9 INNOVATION IN THE BIOPHARMACEUTICAL PIPELINE Mapping Common Cancer Pathways: Genetic Profiling of Colorectal Cancer and Other Tumors May Reveal New Cancer Treatments Colorectal cancer is the fourth most common cancer, and some 50,000 Americans die from the disease each year. Recent research by a national consortium of 150 researchers at dozens of institutions brought together through the Cancer Genome Atlas (CGA) project provided new insights into the complex cascade of genetic abnormalities that are associated with colorectal tumors.

The study systematically analyzed the genetic irregularities in over 200 tumors, identifying common pathways and their frequency. This comprehensive analysis provides insights into the biology of colorectal cancer and identifies potential therapeutic targets and approaches, such as a combination of existing drugs that targets effects related to genetic mutations that also occur in other cancers, such as melanoma.

As researchers gain deeper understanding of how genetic alterations operate across many cancers through common genetic pathways, they will be better able to identify potential new drug targets. The CGA project plans to profile genomic changes in 20 cancer types. To date, results have also been published on glioblastoma and ovarian cancer, and studies of lung cancer, breast cancer.

Executive Summary The U. S. innovative biopharmaceutical industry leads the world in the development of new medicines: over the past decade some 300 new prescription medicines have been approved for use by the U. S. Food and Drug Administration (FDA). …

ABSTRACT INCREASING COMPETITIVE CONDITIONS AND CHANGING ENVIRONMENT CIRCUMSTANCES HAVE FORCED MANY OF TODAY’S FIRMS TO RETHINK THEIR INNOVATION MANAGEMENT STRATEGIES. TO ADDRESS THE CHALLENGES THEY HAVE CHOSEN TO MOVE FORWARD TO A MORE OPEN INNOVATION APPROACH BY USING EXTERNAL SOURCES. …

1. 1 Research problem Today, innovation is identified as one of the most important drivers for companies to succeed with, prosper and sustain continued growth and high profitability. The emphasis usually lies on how to innovate and how the innovation …

1. PHARMACOLOGY IS: Traditional (Broad) Definition “the science of pharmacological agents” Modern (Narrow) Definition “the science of drugs” 2. A DRUG IS: “a chemical substance, not part of the normal diet, which affects an organism’s physiology. ” Broad Definition “any …

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